The long-term goals are to understand the biochemical morbidity surrounding obstructive sleep apnea syndrome (OSAS) to define better the need for treatment and to determine modifiable risk factors for the disease. In this proposal our hypothesis is that sleep-related hypoxemia results in alterations in metabolic regulatory peptides, specifically insulin and insulin-like growth factors (IGF-2), which are known or suspected factors for obesity and disorders such as hypertension, glucose intolerance, and atherosclerosis. Surveys of clinic populations at three sites (Cleveland, Detroit, and Toronto) will characterize the relationship between body habitus, parameters of sleep-disordered breathing, indices of oxygenation, and insulin resistance, defined by fasting serum levels of glucose and insulin in men and women with suspected sleep apnea. Serum levels of IGF-1 and IGF-2 will also be monitored to assess the relative presence and impact of these regulatory prptides in these patients before and, if indicated, after treatment. Physiologic protocols will examine the insulin axis during sleep and will include additional measurements over time of catecholamines, cortisol, glucagon, growth hormone, free fatty acids, and lipid profiles before and after treatment. In these additional studies we will examine patients with known moderate to severe OSAS and results will be compared to age-, sex-, weight-, and body-composition-matched control subjects. Complementary in vitro studies will identify potential cellular mechanisms by which low levels of oxygen trigger production and release of polypeptides such as IGF-1 and IGF-2 and/or alter IGF/insulin receptor function. Results will provide insight into the role of metabolic regulatory peptides in the pathogenesis of sleep-disordered breathing and the mechanisms for this association.